Cyclodextrins are cyclic molecules consisting of 1-4 linked alpha-D-glucopyranose monomeric units. The cyclodextrins containing 6-, 7-, and 8-glucose units joined to form a ring, commonly known as alpha-, beta-, and gamma-cyclodextrin, respectively, are the most important cyclodextrins to date, possibly because of their availability relative to cyclodextrins of different ring size. The usefulness of these cyclodextrins arises from their ability to reversibly form inclusion complexes, or clathrates, with many types of compounds. Inclusion complexes arise when a host molecule, such as a cyclodextrin, has a structure containing an interior cavity into which guest molecules can bind by weak interactions such as van der Waal's forces. The latter are short range forces which are sufficiently strong to allow the formation of definite, generally solid complexes, but are sufficiently weak to permit ready dissociation of the complex to a host and guest molecule.
The cyclodextrins are doughnut-shaped molecules with an interior cavity whose size and shape are determined by the number of glucose units that make up the ring. In alpha-cyclodextrin the almost cylindrical cavity is approximately 7 angstroms deep and 5 angstroms in diameter. In beta-cyclodextrin the depth is the same but the diameter is 7 angstroms, and in gamma-cyclodextrin the cavity is again 7 angstroms deep but is 9 angstroms in diameter. Cyclodextrins are soluble in water because of the many hydroxyl groups of the glucose subunits that surround the rim of the cavity. However, the interior of the cavities is hydrophobic, and it is these hydrophobic cavities which lead to extraction of organic molecules from aqueous solution if the organic materials have the correct shape and hydrophobic character.
The complexing ability of cyclodextrins lends itself to various uses. For example, the cyclodextrins are used in encapsulating desirable flavors and fragrances which can then be stored for reasonably long periods of time and added to foods at their preparation. Reciprocally, cyclodextrins may be used in removing undesirable flavors and fragrances from food by complexing with them. Cyclodextrins also are used in the protection of foods against oxidation, photochemical degradation, and thermal decomposition. These and other uses have been summarized by J. Szejtli, Starch, 34, 379-385 (1982)
Although in some applications the use of the water soluble cyclodextrins themselves is appropriate, in other cases it is desirable to employ an insolubilized cyclodextrin to more readily enable its extended use or to enable its incorporation in a continuous process. For example, when cyclodextrins are employed for their ability to separate various components, as in gas phase chromatography or high pressure liquid chromatography, the water soluble cyclodextrins have obvious limitations and some sort of solid phase incorporating the cyclodextrins is needed. Another example is the use of cyclodextrins to remove bitter components in citrus juice where it is desired to pass the juice over a solid bed incorporating cyclodextrins to give an effluent of reduced bitterness.
These needs previously have been recognized, and one general solution is the preparation of polymeric cyclodextrin derivatives as resins which can be used per se as a solid support in chromatographic applications or as a fixed bed in continuous processes. Buckler et al. in U.S. Pat. No. 3,472,835 recognized the need for insolubilized cyclodextrins as "molecular sieves" in separation and purification processes and offered as a general solution insoluble resins prepared from the reaction of cyclodextrins with compounds having at least two hydroxyl-reactive functional groups per molecule. The patentee disclosed a large class of suitable polyfunctional compounds, including isocyanates, and exemplified several insoluble polymeric cyclodextrin derivatives suitable for use in numerous described applications.
More recently Mizobuchi prepared and tested cyclodextrin polyurethane resins as gas phase chromatographic columns (J. Chromatography, 194, 153 (1980); ibid., 208, 35 (1981)) in the separation of numerous classes of materials, including aromatic amino acids, and as sorbents for low molecular weight organic vapors (Bull. Chem. Soc. Jpn, 54, 2487 (1981)) and aromatic compounds in water (ibid., 55, 2611 (1982)). The resins generally were prepared by reacting at 80.degree.-115.degree. C. a cyclodextrin with from about 3.5 to about 12.6 molar proportions of a diisocyanate in pyridine or dimethylformamide as a solvent, then precipitating the formed resin with a large excess of methanol or acetone. In some cases the unreacted hydroxyl groups in the resins were then silanized. The isocyanates used were hexamethylene diisocyanate, 1,3-bis(isocyanatomethyl)cyclodexane, and 1,3-bis(isocyanatomethyl)benzene.
As useful as are the polymeric resins themselves as the solid adsorbent, they have limitations arising from porosity and transport characteristics. That is, the size and number of the channels in the solid resins limit transport of species in solution to available cyclodextrin sites and consequently restrict the efficiency of separation. It was reasoned that such transport limitations would be appreciably relaxed, if not removed, if the cyclodextrin polymer was presented as a thin film. The problem to be addressed then is the preparation of thin films of cyclodextrins. However, not just any thin film will suffice; both the method of preparing these thin films and the properties of the films themselves must meet several criteria for optimal film usage as we envisage it. A thin film of cyclodextrin polymers should be able to be formed on virtually any surface. The method of forming the thin film should be convenient, facile, inexpensive, and universal-that is, the same method should be applicable regardless of the nature of the surface. The resulting film should be insoluble in water and in most organic solvents other than dipolar aprotic solvents so that it is retained under process conditions. The film also should be tough, abrasion-resistant, and tenacious so that it continues to function effectively in, e.g., a fixed bed environment of high, turbulent fluid flow.
The problem is simply stated; its solution is our invention. More particularly, we have found a class of lightly crosslinked cyclodextrins with a solubility in water under about 200 ppm and with a solubility in an organic solvent to the extent of at least 0.1 weight percent. This differential solubility of the lightly crosslinked cyclodextrin enables thin films to be cast on a surface and is an indispensable feature of, and a key to, our invention. These crosslinked cyclodextrins share the property of forming a film with good adhesion to virtually any solid phase substrate, with the film being resistant to peeling and abrasion when the coated substrate is used as a fixed bed in, for example, separation processes. The lightly crosslinked cyclodextrins of our invention also share the property of forming inclusion complexes to an extent similar to the non-crosslinked cyclodextrin, and the films are relatively simple to prepare using commonly available materials. Among the lightly crosslinked cyclodextrins we have examined, polyurethane cyclodextrins have desirable features from other aspects, which led us to develop a method for making coatings of cyclodextrins crosslinked with polyfunctional isocyanates. The method is extraordinarily versatile, almost approaching universality, and can be used to coat materials as diverse as ceramics, fabrics, metals, paper, wood, and glass.
The cyclodextrin resins of Buckler et al., or "insolubilized cyclic dextrins" as the patentees refer to them, appear to be highly crosslinked cyclodextrins with low water solubility and, judging from the examples, low solubility in organic solvents. Certainly it can be said that the patentees have no appreciation of the differential solubility characteristics of the lightly crosslinked cyclodextrins of our invention, nor is their any contemplation of the important film-forming properties associated with this differential solubility. The patentees of U.S. Pat. No. 3,477,802 teach modifying polymeric materials having active hydrogen atoms, such as naturally occurring polysaccharides, with saturated beta oxyethyl derivatives of activated olefin compounds containing at least one activating group in a position beta to an ether or a hydroxyl oxygen. Such modification by a monofunctional reagent does not afford a lightly crosslinked polymer, and does not appear relevant.
Wimmer, U.S. Pat. No. 2,910,467, teaches that starch crosslinked with hexahydro-1,3,5-triacryloyl-s-triazine affords an improved adhesive of increased water resistance. Smith et al. disclose lightly crosslinking starch adhesive compositions with polyfunctional reagents to increase the resistance of such adhesives to loss of viscosity produced by pumping, stirring, etc.; U.S. Pat. No. 3,004,855. The patentees of U.S. Pat. No. 4,438,262 teach that the cyanoethylation product of dihydroxypropylated polysaccharides are high dielectric compounds with superior adhesiveness. Among various applications of use are mentioned film, sheet, coating film and plasticizer, and the patentees make mention of utilizing their dielectric properties by forming a thin film for electroluminescent panels.
From this review of the prior art applicants believe that coatings from cyclodextrins appear not to have been fairly taught. In particular, coatings from cyclodextrins lightly crosslinked by the polyfunctional reagents of this invention and having the differential solubility characteristics, described within, necessary for the success of our invention have not previously been alluded to. Even more important is the fact the coatings of our invention result from only a narrow window of resin-forming conditions nowhere taught or contemplated, with the possibility of coating materials according to our invention never even recognized.